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Once a pharmaceutical, medical device manufacture or bio-technology company has developed a treatment, device or drug therapy, approval from a regulatory authority, such as the FDA in the US, must be obtained before it can be made available through prescription. The submission to the regulatory authority consists of a large volume of information, including clinical information which focuses on the safety and efficacy of the therapy. Much of that information is collected by conducting clinical trials.
A pharmaceutical, medical device manufacture or bio-technology company sponsors a series of clinical trials. Either an internal clinical group manages these trials or they are out-sourced to a clinical research organization (CRO). The clinical group or CRO contracts with investigation sites that in turn recruit patients for the study and collect the clinical data.
The clinical trials are performed in a series of phases, known as Phase I, Phase II, Phase III, and Phase IV. Each phase varies in duration, the number of patients involved and purpose. Failure at any stage of Phases I, II or III of the clinical trial process effectively ends the therapy""s chances for final approval.
Before entering Phase I, the sponsor needs to obtain regulatory approval. Phase I trials typically last six months and involve tens of volunteer subjects usually all of whom are located at a single investigative site. Phase I trials test the safety of the therapy. Once Phase I rials are complete and the therapy has been shown to be safe, the sponsor requests permission from the regulatory authority to proceed with further clinical tests.
Phase II trials typically last six to twelve months, involve tens to hundreds of patients and are conducted to test the effectiveness of the treatment, device or drug. A sponsor may conduct many Phase II trials, attempting to find as many uses of the therapy as possible. If the therapy appears to be effective, the sponsor requests permission from the regulatory authority to proceed with large scale trials.
For each likely use of the therapy, the sponsor conducts at least two Phase III trials. Phase III trials typically last 24 to 36 months and involve thousands of patients. Phase III trials are blinded trials, that is, a portion of the patients receive the therapy and the remaining patients receive a placebo or active control, and the identities of patients taking the trial therapy are not known to anyone until the trial is complete. Phase III trails are conducted to test the safety and effectiveness of a therapy in a large population. The Phase III trial is the first opportunity to observe infrequent adverse effects in the general population; each and every one is carefully recorded. Since the effectiveness of the therapy is tested in a blinded environment, the results are not known until after the study is complete.
Phase IV trials occur after approval and are generally held to obtain approval to change a characteristic such as the delivery system, e.g., from liquid to tablets, or to change the status, e.g., from a prescription drug to an over-the-counter drug. Failure at any stage of a Phase IV trial effectively ends the therapy""s chances of obtaining approval for such a change.
Every clinical trial has a protocol which specifies the exact timing and nature of the measurements and interventions to be performed on each patient. The protocol""s time-line lists a series of events, or visits, where the data are collected from the study patient. The time-line of a typical study starts with the screening and enrollment of a patient and typically ends with the last patient visit.
FIG. 1 illustrates the preparation and processing of paperwork in a typical clinical trial. There are a number of points in the process where the data are audited and reviewed. A patient 401 visits the investigative site 413. For each visit, the protocol instructs the investigator to collect certain information 403 about the patient 401. After the information 403 is collected, it is recorded on a Case Record Form (CRF) 405. Periodically, a Clinical Research Associate (CRA) 417 visits the investigative site 413 and compares the data in the original medical record 403 with the information on the CRF 405. This process 406 is known as source document validation, or SDV.
Once the CRF has been source document verified, CRF 405 is delivered to the organization 407 running the trial (either a CRO or an internal clinical group at he sponsor) as indicated by arrow 408. When the CRF 405 arrives at the sponsor/CRO 407, its data is entered into a clinical database 409 twice to ensure that no errors are introduced, as indicated by arrows 410A and 410B.
A medical monitor 415 and clinical data manager (CDM) 419 at the sponsor/CRO 407 examine the CRF 405 to look for inconsistencies. If any of the data are incomplete or appear incorrect, the CRF is sent back to the investigative site 413 with a query 411 for correction, a process known as cleaning. If someone at the investigative site 413 makes a change as a result of a query 411, the data is again source document verified by the CRA 417, and is sent back to the sponsor/CRO 407 for data entry, as identified by arrow 412. When all of the data cleaning is complete, the clinical database 409 is locked and data analysis begins.
As can be seen, a large volume of data is collected during each clinical trial, and the collection and management of clinical data is a large problem that requires many people performing a number of different and unique roles. These roles fall into three groups: the investigative site roles, the clinical data review roles, and other central sponsor roles.
Implementing such a system or method on the Web has the obvious advantage of easexe2x80x94many people are now familiar with Web technology and even those with computerphobia are becoming comfortable accessing the Web. In addition, because browsers are so inexpensive, while the personal computers on which they run can typically be had for under $1,000, there are no major expenses involved for other than the development of the clinical trial database. No special software needs to be distributed.
On the other hand, one disadvantage is that access over the Web can be considerably slower than a direct connection to a host server. Another is that certain things that can be done easily in a closed environment with custom software, such as curved boundaries between frames, are not so readily done on the Web. The present invention is aimed at overcoming these and other disadvantages.
Therefore, a method of implementing a graphical user interface (GUI) control element within a client browser, comprising creating several bitmaps which can be constructed to present the GUI control element in a variety of different states. A Standard Generalized Markup Language (SGML)-derived language such as HTML or XML is used to specify placement of the bitmaps within a document. Upon receipt of the document, a browser displays a desired GUI control.
Preferably, placement of he bitmaps is specified by placing indicators such as URLs corresponding to the bit maps in certain locations, preferably table entries, within the document, such that the browser will correctly display the control element. Preferably, these bit maps are used by many similar GUI Controls.
Furthermore, a bitmap may be partitioned into multiple sections, where each section is associated with a different indicator.
In particular, in a preferred embodiment, one type of control element is a button control which comprises left, right, top and bottom pieces. A label is placed between the top and bottom pieces.
Another type of control element is a file tab, or tab, control, comprising left, right, top and bottom pieces. A label is placed between the top and bottom pieces. Multiple tab controls can be grouped together, sharing bitmaps which have a left or right overlapping piece. Different bitmaps also provide different styles such as color to portray a selected or non-selected tab.
Yet another type of control is a linear control which comprises button control elements spaced at intervals along a line. Each button control element has a corresponding bit map or combination of bit maps. A pointer indicating a current value along the line also has an associated bitmap.
In the preferred embodiment, the server is stateless with respect to the GUI controls. That is, when a request is received, the server has no knowledge of he states of the controls other than what is sent in the request.
The present invention also provides a method of entering clinical trial data from a client, where the data is maintained on a server. A data entry form to be displayed at the client, is generated at the server dynamically in a SGML-derived language, from a library of code fragments. The form is generated according to the user, the patient, the protocol version within a clinical trial and data previously entered.
In a preferred embodiment, a protocol, or clinical, database is created which is specific to an application. A data database is created which is specific to a subject processed by the application. Then the form is generated based on the protocol database, preferably based on a clinical protocol, and a context received from the client. Preferably this is done by generating a template based on the protocol database and a context received from the client. The form or template is populated with application data from he data database, and published to the requesting client browser.
Preferably, the template comprises several frames including control frames with one or more control elements. An intermediate frame presents a visual attribute shared by the control frames. The appearance of the intermediate frame depends on the visual appearance of the control frames.
In addition, in a preferred embodiment, protocols can be changed during the trial. The generation of the template is then further based on the protocol version which was active at time of entering data to be displayed. Thus the form to be displayed is itself based on the protocol version which was active at time data was entered.
Furthermore, in a preferred embodiment, rules are associated with the displayed form, and are based on he protocol version which was active at the time of entering data to be displayed in the form.
Yet another aspect of a preferred embodiment of the present invention is the discouragement of inadvertent use of a computer application, by requiring a log-on procedure for each user, and displaying a picture of the currently logged-on user.
Still another aspect of a preferred embodiment of the present invention is the provision of context-sensitive help. Preferably, a displayed form has at least one question to which a user must respond to provide clinical data. Links are created between the text of each question and detailed information related to the question. If the user clicks on text of the question, detailed information corresponding to the question is retrieved from the server is displayed.
Preferably, the detailed information is derived from any or all of three source documents defining the clinical trial: a protocol document, an investigative brochure, and a study guide. Preferably, the user can walk through each of he documents.
Another aspect of the present invention is the dashboard screen which provides information regarding the trial, customized for the user and presented to the user upon logging in to the system. Such information preferably includes but is not limited to trial-related news, alerts, statistical information, progress reports and a list of work to be completed